Hair Follicle Cells Drive Psoriasis Inflammation

HAIR follicle cells may contribute to psoriatic inflammation through a molecular pathway involving S100A1, with findings highlighting a potential mechanism underlying the particular susceptibility of the scalp to psoriasis.

Researchers integrated bulk, single-cell and spatial transcriptomic data from healthy and psoriatic human skin across multiple anatomical sites to investigate the role of hair follicle cell subsets. Five populations were identified, including K15^hi stem cells, K17^hi, SPINK5^hi, K23^hi and MT2A^hi hair follicle cells.

Among these populations, K17^hi hair follicle cells were markedly expanded in both perilesional and lesional psoriatic skin. They also showed preferential distribution along a trajectory associated with pro-inflammatory programmes.

K17hi Cells Showed Pro-Inflammatory Activity

Healthy scalp skin contained greater numbers of hair follicle cells and was particularly enriched for K17^hi cells compared with other anatomical sites. This enrichment was further increased in scalp psoriasis.

S100A1 was the most highly differentially expressed gene identified in K17^hi hair follicle cells. The researchers found that its expression was regulated by transcription factor TCF12 and that S100A1 mediated annexin A2 (ANXA2)-dependent CD4+ T-cell activation and tissue-resident memory features.

Experiments investigating K17 further supported an upstream role for the TCF12-S100A1 pathway, while blocking ANXA2 reduced S100A1-induced T-cell responses.

S100A1 Targeting Reduced Inflammation

The findings were further supported in an in vivo mouse model of psoriasiform inflammation. Topical knockdown of S100a1 alleviated imiquimod-induced inflammation, suggesting that the pathway may have therapeutic relevance.

The researchers concluded that K17^hi hair follicle cells form a regionally enriched pro-inflammatory niche that contributes to psoriasis through the TCF12-S100A1-ANXA2 follicular-immune axis.

Targeting this pathway could therefore represent a potential therapeutic strategy for difficult-to-treat psoriasis, although the findings currently provide mechanistic rather than clinical evidence.

Reference

Tang X et al. K17^hi hair follicle cells orchestrate psoriatic inflammation through S100A1-dependent signaling. Br J Dermatol. 2026;DOI:10.1093/bjd/ljag43.